Although the bacterial population living inside our gut is more or less stable once we reach adulthood, in women it can be affected by hormonal changes. In other words, it can change with pregnancy, menstruation or menopause. In today’s article we’re going to talk about the microbiota and how it influences the early stages of gestation.
What is the microbiota?
The microbiota is the set of beneficial bacteria in our body. They have different functions: protection against pathogens, development and maturation of our immune system, digestion of nutrients and production of vitamins, among others. We have ten times more bacteria than human cells.
What do we know as the microbiome?
The microbiome is the set of genes contained in all the microorganisms that make up the different microbiotas of the human body and that relate to the genome itself.
An adequate microbiome at the level of the reproductive tract is associated with good reproductive and obstetric outcomes. Our reproductive tract is dominated by lactobacilli. Lactobacilli produce antimicrobial peptides, anti-inflammatory cytokines and lactic acid, which favour optimal microbial homeostasis. Under dysbiosis, there are fewer lactobacilli and other bacteria appear to a greater or lesser extent, giving rise to disease.
There are exogenous and endogenous factors that can affect the microbiota of the genital tract:
- Hormonal status
- Race
- Antibiotic use
- Sexual habits
- Diet
- Obesity
- Tobacco
Bacterial vaginosis and fertility
We speak of bacterial vaginosis when the number of lactobacilli in the vagina decreases and the number of anaerobic bacteria increases. Infertile women have a bacterial vaginosis prevalence of 39%.
The pregnancy rate after in vitro fertilisation is also lower in the presence of vaginosis. It has also been associated with a higher prevalence of preterm birth and premature rupture of membranes.
At the endometrial level, a microbiota with a predominance of lactobacilli is associated with better implantation rates and a lower miscarriage rate.
Relationship between microbiota and miscarriage
Recent studies have observed that women who experience first-trimester pregnancy loss unrelated to chromosomal abnormalities more frequently have a vaginal microbiome poor in lactobacilli. It has also been seen that the risk of miscarriage is higher in cases with a greater predominance of streptococci.
Both the presence of streptococci and of Prevotella, in women with euploid miscarriage, are associated with an increase in the production of pro-inflammatory cytokines such as IL-6, IL-1beta, IL-18 and TNF-alpha.
In contrast, a predominance of lactobacilli, especially Lactobacillus crispatus, is associated with greater bacterial stability in the vagina and a lower activation of the local immune response during gestation.
For this reason, it appears that the interrelationship between the vaginal microbiota and the local immune response in early gestation determines the extent of the inflammatory response and is related to the risk of miscarriage.
While we don’t yet know whether this pro-inflammatory response, mediated by the presence of a lower proportion of lactobacilli and a high diversity of other bacterial species, could be the target of some intervention, it could potentially benefit from the use of antibiotics or probiotics that might reduce the risk of miscarriage or implantation failure.
Relationship between gut microbiota and fertility
It’s not only the microbiota of the genital tract that matters at the time of implantation and in the early stages of gestation. The gut microbiota has also been shown to play an important role as a modulator of the immune response, and intestinal dysbiosis is involved as a risk factor for triggering inflammation.
Intestinal dysbiosis alters the integrity of the gut barrier, allowing the entry of various antigens, endotoxins and pathogens, as well as an altered production of neurotransmitters and metabolites such as short-chain fatty acids, which lead to inflammation.
On the other hand, there is a clear relationship between the microbiota of the gastrointestinal tract and the uterine microbiota and vaginal ecosystem. Intestinal dysbiosis exerts a significant influence on vaginal and endometrial dysbiosis and is involved in the immune response, promoting a pro-inflammatory state. All of this has a significant impact on fertility and on the early stages of gestation.
A better understanding of the impact of gut flora at the reproductive level opens the door to new strategies for preventing and treating infertility and other associated conditions, such as dietary changes, the use of probiotics or supplementation with prebiotics.
And that’s all for today’s article. At Clínica Fertia we help all couples and women who dream of becoming mothers. If you too have undergone several assisted reproduction treatments without success, contact us to study and analyse your case on a personalised basis.
Bibliography
1. Gaggiotti-Marré S, Alvarez M, Gonzalez-Foruria I, Parriego M, Garcia S, Martínez F, et al. Low progesterone levels on the day before natural embryo transfer are negatively associated with live birth rates. Hum Reprod. 2020;35:1623-1629.
2. Labarta E, Mariani G, Rodriguez-Varela C, Bosch E. Individualized luteal phase support normalizes live birth rate in women with low progesterone levels on the day of embryo transfer in artificial endometrial preparation cycles. Fertil Steril. 2021;117:96-102.
3. Thompsen LH, Kesmodel US, Erb K, Bungum L, Pedersen D, et al. The impact of luteal serum progesterone levels on live birth rates – a prospective study of 602 IVF/ICSI cycles. Hum Reprod. 2018;33:1506-1516.
4. Tu J, Lin G, Gong F. Additional luteal support may improve IVF outcomes in patients with low progesterone level in middle luteal phase following a GnRH agonist protocol. doi.org/10.1080/09513590.2020.1756252.
